All living things are made up of thousands upon thousands of cells.
These microscopic building blocks of life come in many different forms and work together to create the organs and tissues of all multicellular organisms.
In order for cells to function the way they do, they need to be able to take in molecules and substances from the blood.
Oxygen and glucose are just two examples of substances that cells need to be able to absorb to facilitate the chemical reactions necessary for energy production and survival.
As well as taking in molecules, they also need to be able to excrete waste products that would cause harm if allowed to stay.
Endocytosis and Exocytosis are two of the processes that cells can use to let useful substances cross over the cell membrane, and expel waste back into the extracellular fluid.
In this article we will explain what endocytosis is, the three different mechanisms by which it can occur and how it differs from exocytosis.
What Is Endocytosis?
Endocytosis refers to the means by which molecules and ions that would not normally be able to pass through the cell membrane enter the cell.
The cell membrane is composed of a phospholipid bilayer, with special proteins embedded into the surface.
This bi-layer is semi-permeable, meaning it will allow some things to pass through while inhibiting others.
Endocytosis works by a process called invagination.
A molecule that cannot pass through the phospholipid bilayer due to its size or polarity attaches itself to the outside of the membrane.
The membrane then curves inwards towards its own cytoplasm at the site where the molecule has attached.
This creates a dent in the cell that slowly expands to engulf the molecule or substance that needs to be absorbed.
Once the molecule in question has been fully engulfed, the bubble of cell membrane it is contained in pinches off from the main phospholipid bi-layer to form a self-contained package called a vesicle.
At the same time, the two ends at the top of this bubble join together to restore the cell membrane back to its original shape.
There are three different methods by which endocytosis can take place, each of which will be covered in depth in later sections.
Is Endocytosis A Form Of Active Or Passive Transport
Passive transport, or passive diffusion as it is also known, is the means by which most molecules and ions enter or exit the cell by following a concentration gradient.
This means that the molecules move from an area where they are highly concentrated to a region of lower concentration.
Passive transport allows things to both enter and leave the cell, and requires no energy to take place.
Endocytosis on the other hand is a form of active transport.
This means that in order for it to take place, the cell needs to use energy generated from the breakdown of adenosine triphosphate (ATP).
When ATP is converted into adenosine diphosphate (ADP), energy is released that can be used to initiate the process of endocytosis.
Both endocytosis and exocytosis will only occur in one direction, and as such, molecules are only capable of entering the cell via endocytosis.
Of all the different methods of endocytosis, phagocytosis is the most well understood by scientists.
This process is used by numerous cells that work as part of the immune system, including macrophages, and dendritic cells.
These cells use phagocytosis to engulf harmful bacteria, or pathogens that could cause disease.
Once inside the cells, these harmful organisms can be destroyed before they cause any further harm to the body.
Cells that are capable of engulfing toxins and pathogens are known as phagocytes, and they need to be activated before they can do their job.
White blood cells are drawn to the site of an infection by chemical messengers called cytokines.
Via a process called chemotaxis, the phagocyte literally follows the cytokine through the body to the area where it is needed.
Phagocytes are capable of manipulating their cytoplasm to change the shape of their cell membrane.
This allowed them to create arm-like extensions, called pseudopodia, that can reach out and wrap around invading organisms to engulf them.
But how does the phagocyte know what to absorb?
At the site of an infection, special antibodies called oposins will bind to the surface of an invasive pathogen or antigen (a foreign body that triggers an immune response).
Phagocytes have a high affinity for these oposins, which means they will be drawn towards them.
The oposin basically acts as a chemical signpost that indicates a specific molecule or antigen needs to be absorbed and destroyed by phagocytosis.
Cells that have been infected may also be marked by antibodies in a similar fashion.
These cells will be engulfed by the phagocyte and destroyed to prevent them from contaminating other cells.
Recognizing the target molecule or antigen is only the first step of phagocytosis. Once the phagocyte has identified its target, it moves to make contact with it.
Once the pathogen touches the cell membrane of the phagocyte, it activates specialized proteins that trigger the cell to begin endocytosis.
These receptors cause the cells to start manipulating and altering the shape of its cell membrane.
This is achieved through the polymerization of actin, which leads to the creation of pseudopodia that reach around the target molecule.
Studies have shown that the protein myosin helps to manipulate the actin filaments, causing the cell membrane to change shape in such a drastic way.
Eventually the antigen or molecule will be completely surrounded, at this point two things happen.
The two pseudopodia that reach around to engulf the foreign body meet in the middle and fuse together.
This allows the cell membrane to reseal, while at the same time trapping the target molecule or antigen in a special vesicle called a phagosome that is held within the phagocyte.
The phagosome bonds to a special organelle called a lysosome.
This contains special enzymes, free radicals and other substances that break down the engulfed pathogen and digest it.
Finally, after the foreign body has been completely destroyed, its remains are ejected from the phagocyte by exocytosis.
Phagocytosis is commonly referred to as cell eating, while pinocytosis is known as cell drinking.
This is the process by which a cell ingests parcels of extracellular fluid along with dissolved ions and minerals.
It works in a similar way to phagocytosis, but with key differences in how the vesicles form to engulf the desired molecules.
Instead of aiming to destroy the ingested material, the molecules absorbed into the cell by pinocytosis are used to feed the cell.
They may be used to repair damaged organelles or required to take part in chemical reactions within the cell itself.
Unlike phagocytosis, pinocytosis is a continual process, however it still happens as a response to certain substances.
These substances can include sugars, minerals and ions dissolved in the extracellular fluid that the cell wants to absorb for its own nutrition and benefit.
The receptors that trigger pinocytosis are not specific and can respond to several types of stimuli present in the extracellular fluid.
When desirable molecules bind to these receptors, they trigger the invagination process.
While phagocytes use pseudopodia to surround and engulf their targets, cells engaging in pinocytosis use a different method.
Instead, the membrane sinks into the cytoplasm of the cell, forming pits in the cell membrane.
These pits slowly expand to wrap around the extracellular fluid that contains the desirable molecules.
As it sinks in, a bubble is slowly formed around this region of extracellular fluid.
Once the area has been completely surrounded, a vesicle pinches off into the cytoplasm and the ends of the pit meet to reseal the cell membrane.
The receptors that trigger pinocytosis are connected to a special protein called clathrin which is located on the cytoplasm side of the cell membrane.
Clathrin works alongside other proteins to form the pit or dent in the cell membrane that initiates invagination.
As such, the materials absorbed by pinocytosis sink into the cell, rather than the cell reaching out for them as we saw in phagocytosis.
Once the vesicle pinches off from the cell membrane, it travels through the cytoplasm to fuse with the lysosomes in the cell.
These lysosomes then release enzymes and other substances for digesting and absorbing the nutrients and molecules contained in the vesicle.
There are two main types of pinocytosis, depending on the size of the molecules being absorbed.
Macropinocytosis involves the creation of more compact vesicles and heavily relies upon the protein caveolin.
Meanwhile, micropinocytosis is defined by the formation of bigger vesicles that are constructed through the manipulation of actin filaments.
Differences Between Phagocytosis And Pinocytosis
Before we move on to the third method of endocytosis, we thought it would be best to highlight the crucial difference between phagocytosis and pinocytosis.
The similarities between the two processes can make it difficult to understand how different they really are.
One of the biggest differences between these two methods of endocytosis is how the material is engulfed into the cell.
In phagocytosis, pseudopodia form due to the manipulation of actin filaments.
These arm-like extensions of the cytoplasm and surrounding membrane wrap around the target molecule to surround and engulf it.
Meanwhile, in pinocytosis, desirable molecules are subsumed into the cell by the formation of pits in the membrane.
Because of the way that phagocytosis works, it is used to absorb much larger molecules than pinocytosis.
Invasive pathogens, toxic antigens, and even infected cells can all be engulfed by this method.
Meanwhile, pinocytosis involved regions of extracellular fluid being engulfed along with any dissolved minerals or sugars.
As such, the vesicles formed in this process are generally much smaller, since the cell wants to avoid absorbing too much extracellular fluid.
If the cell bites off more than it can chew, then it will risk consuming harmful chemicals or substances as well as the desired molecules that triggered the receptors.
Speaking of receptors, another difference between pinocytosis and phagocytosis is that both use different types of receptor protein.
Phagocytes have specialized receptors that are designed to respond to a specific oposin or antibody.
On the other hand, the receptors responsible for pinocytosis are not specialized at all and can be triggered by a far wider range of molecules and solutes.
This makes sense, as pinocytosis is needed for absorbing more than just one thing, whereas phagocytes should only target cells or organisms that trigger an immune response.
Phagocytosis can only occur in a select group of cells, most of which are connected to the immune system.
There are other cells that can act as phagocytes, but generally all of them will be responsible for attacking foreign bodies, or removing dead cells.
In contrast, nearly all of the cells in a human body are capable of pinocytosis.
This process happens continuously throughout a cell’s lifetime and is one of the primary methods by which cells take in useful substances from the extracellular fluid they are surrounded by.
The final difference between these two processes is that of their purpose.
Foreign bodies engulfed by phagocytosis are destroyed to prevent them causing further harm to the body and other cells.
Meanwhile, substances taken in by pinocytosis are used to signal changes in the extracellular matrix, or provide essential nutrition for the cell to survive.
Now that we have covered these fundamental differences between pinocytosis and phagocytosis, we are ready to move on to the third method of endocytosis.
Receptor Mediated Endocytosis
Much like pinocytosis, receptor mediated endocytosis is responsible for absorbing useful substances that the cell needs.
These include large molecules such as sugars, hormones and anything else that the cell may need, but can’t ingest through passive diffusion.
As the name suggests, this type of endocytosis is facilitated by specialized receptors.
Unlike those used for pinocytosis, these receptors will only respond to a specific substance or molecule.
This gives the cell complete control over how much it ingests and what it is absorbing.
The receptors for this type of endocytosis work similarly to those seen in pinocytosis, except they are much more specific.
These receptors have a ‘Y’ shape, the tail of which penetrates the phospholipid bilayer to emerge in the cytoplasm side of the cell membrane.
Attached to this stem is a special kind of protein called an adaptor protein.
Since the macromolecules being absorbed by this process only respond to a specific type of receptor, they are known as ligands.
Receptor-mediated endocytosis can occur with or without these ligands, however for the purposes of this example we will focus on an incident where ligands are present.
When ligands attach to the receptors, it triggers a reaction on the other side of the cell membrane that causes a phospholipid molecule to bind to the adaptor protein.
The adaptor protein then alters its shape, so it can bind with another protein we have already encountered, clathrin.
Clathrin is a ‘T Shaped protein that can change its shape when adjacent to other clathrin molecules to become spherical.
It is this change of shape that causes the pit in the cell membrane to form, slowly pulling the receptor proteins towards the cytoplasm.
This pit eventually forms a vesicle that is pinched off from the cell membrane by a protein called dynamin.
The cell membrane then refuses, and the vesicle separates into the cytoplasm.
Unlike other vesicles formed by phagocytosis or pinocytosis, the vesicle formed by receptor mediated endocytosis is composed of numerous parts.
As well as the ligands being absorbed, there are also the receptor proteins it is attached to and the adaptor proteins located on the outside attached to clathrin molecules.
As such, all of these different parts need to be sorted and separated from each other before the contents of the cell can be digested by a lysosome.
For this purpose a specialized organelle is required, called an early endosome.
From the moment the vesicle is subsumed into the cytoplasm, the adaptor proteins and clathrin molecules detach themselves.
The vesicle then merges with the early endosome, the inside of which has a more acidic PH than the rest of the cytoplasm.
This acid helps to separate the ligands from their receptor proteins, some of which are repackaged into a different endosome.
The recycling endosome carries receptor proteins back to the cell membrane, where they can be reused.
Meanwhile, the first endosome containing the ligands begins to mature into a late endosome.
Once it has fully developed, the late endosome is ready to merge with a lysosome, so that its contents can be broken down into useful materials for the cell.
During maturation, several changes take place with the endosome that prepare it for merging with the lysosome.
Firstly, any proteins embedded on the outside of the endosome are brought inwards, so they can be broken down by the acid inside.
Then a protective layer forms around the outside of the endosome that prevents enzymes or acidic fluid from escaping into the main cytoplasm of the cell.
This prevents any potential damage to the other organelles in the cell.
Finally, in preparation for binding with the lysosome, proton pumps in the membrane of the endosome bring in hydrogen ions to lower the PH even further.
This provides an optimal environment for the enzymes in the lysosome to break down the ligands into smaller chemicals and molecules.
This allows the ligand to be used by the cell for important chemical reactions and functions.
Exocytosis And How It Differs From Endocytosis
Now that we have covered the three different types of endocytosis, the only thing left to cover is exocytosis.
This is the process by which waste products and other molecules that the cell doesn’t need are expelled into the extracellular fluid.
It can also be used to allow cells to communicate with each other. One cell releases a stimulus via exocytosis that can be picked up by another cell via endocytosis.
Molecules that are ejected out of the cell in this way first need to be packaged into a vesicle.
However, instead of a vesicle forming from the invagination of the cell membrane, it is done in this instance by an organelle called the Golgi apparatus.
The Golgi Apparatus
Two of the main things that commonly pass through the Golgi apparatus are lipids and proteins created by the rough endoplasmic reticulum.
However, this organelle serves a variety of other functions as well, including the creation of new lysosomes.
The Golgi body is made from layers of phospholipid membrane arranged in a way that looks like a pile of empty sacks.
As molecules pass through these sacks, enzymes are attached to the proteins, lipids and other substances contained within.
These enzymes help the Golgi apparatus to sort through its various cargo, so it knows what needs to be sent where.
This also allows it to know if it has received molecules by mistake that need to be sent back to the rough endoplasmic reticulum.
Once sorting has occurred, the molecules leave the Golgi body.
Small pieces of the Golgi apparatus pinch off to form vesicles containing the cargo that needs to be transported elsewhere in the cell.
These vesicles may move to the lysosomes so that their contents can be broken down and digested. Alternatively, they may move to the cell membrane.
Some vesicles will contain new transporter proteins or ion channels for embedding in the cell membrane, while others will contain molecules that need to be ejected from the cell by exocytosis.
This is another form of active transport, which means that it requires energy to occur.
Transport vesicles from the Golgi apparatus or other parts of the cell arrive at the cell membrane and fuse with it to expel their contents into the extracellular fluid.
Just like with endocytosis, there are few different mechanisms by which exocytosis can take place.
The simplest method is one we have already mentioned, whereby a transport vesicle merges with a lysosome so that its contents can be broken down and integrated into the cell.
However, both regulated and constitutive exocytosis will require the vesicle to fuse with the cell membrane so that their contents can be released into the extracellular fluid.
For both mechanisms, the first step is for the vesicle to be transported along microtubules of the cytoskeleton to the cell membrane.
Here the next step can take place, which is called tethering.
This is when the transport vesicle touches the inner surface of the cell membrane and the phospholipid bi-layer of the two membranes begins to merge.
All of these steps are shared by both constitutive and regulated exocytosis.
However, after this point, the two processes start to differ.
Constitutive exocytosis is similar to pinocytosis in that it is a continuous process that does not require a specific stimulus to take place.
When a vesicle fuses to the membrane in constitutive exocytosis, it undergoes what is known as kiss and run fusion.
This means that the vesicle only partly merges with the membrane, just enough to form a fusion pore, so its contents can be released into the extracellular matrix.
Once this is done, the membrane reseals and the vesicle pinches back off to return to the Golgi apparatus.
Regulated exocytosis occurs due to external stimuli triggered by receptor proteins on the outside of the cell membrane.
When these stimuli are detected, complete fusion takes place. In complete fusion, the vesicle completely merges to become part of the cell membrane itself.
There is one other type of exocytosis that can take place, called compound exocytosis. This involves the exocytosis of multiple vesicles at the same time.
One of the simplest ways this can occur is by the vesicles merging together to form an extra-large package which then fuses with the membrane.
Alternatively, when a single vesicle has fused with the membrane to form a fusion pore, other vesicles can start to fuse with it, thus extending the pore.
As you can see, both endocytosis and exocytosis are very similar processes that are separated by crucial differences.
In endocytosis the vesicle is formed from the invagination of the cell membrane, while in exocytosis it is formed by the Golgi apparatus.
Endocytosis and exocytosis are complex processes that involve many different steps.
However, understanding them will go a long way towards understanding how cells take in and expel molecules.
This enables the cell to not only take in nutrition and eject waste, but also to communicate with other nearby cells.
You can see the processes of endocytosis and exocytosis at work all around the body, from the liver and pancreas to the synapses between neurons.
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